Preliminary data indicates that in vivo 31P NMR is sensitive to the state of tumor oxygenation and may serve as both a predictor and monitor of tumor response to x-radiation therapy. As a basis for developing this technique for clinical application a series of experiments are proposed in the RIF-1 fibrosarcoma tumor model. This tumor will be examined in the in vivo state, subcutaneously implanted in C3H/He mice, and in the in vitro state, as a dispersed tumor, as spheroids, and anchored to glass or Sephadex beads. Special in vivo probes (equipped with surface coils or with shielded solenoidal coils) and in vitro probes (equipped with a spinfilter or with a chamber for holding immobilized cells) have been developed for this purpose. Changes in 31P NMR parameters (levels of phosphate metabolites and internal pH and 1H NMR parameters (lactate concentration and H2O T2) will be monitored during untreated growth and after x-radiation. The relationship between these parameters and the histological state of the tumor, its degree of oxygenation, and extent of response to x-radiation will be evaluated. Tumor oxygenation will be measured by comparison of aerobic and anoxic dose-response curves for x-radiation, by surface fluorimetry and near IR spectroscopy, by comparison with in vitro tumors at known pO2 conditions and by the effects of metabolic inhibitors. Cell kill will be measured by clonogenic assay and by tumor growth delay. If time and funding permit the ability of NMR to monitor tumor reoxygenation and identify tumors responsive to hypoxic cell sensitizers will also be evaluated.